QUESTIONS

1. N-3 PUFAs are used as anti-inflammatory medications. How do they exert this effect?
    
2. It would be very nice if N-3 PUFAs could be used therapeutically in acute inflammatory events such as sepsis. What has been the biggest problem using N-3s in this setting?
    
3. There's a lot of talk lately about the optimal ratio of N-6 to N-3 PUFAs. Why do we think its the ratio & not straight quantity that's important?
    
4. Assuming this ratio stuff is true, why is the bad news for the makers of Dermcaps?
    
5. What is the difference between Kwashiorkor & marasmus?
    
6. What amino acids are we generally talking about when we refer to the "essential amino acids."
   
   
   
   
    

ANSWERS

1. Arachidonic acid (an N-6 PUFA) lives in cell membranes.  When the appropriate stimulus arises, it is mobilized & used by assorted enzymes to make inflammatory mediators.  The idea in using N-3 PUFAs is that they, too, are taken up by cell membranes & used by enzymes when the stimulus arises but the products created when N-3s feed into the pathways are either not inflammatory or are less inflammatory. N-3 PUFAs decrease availability of the N-6's competitively.
   
   
   
   
    
2. Well, first there really isn't a route of admistration other than the oral route & most such patients aren't eating. (Note TPN solutions are packed w/ N-6 PUFAs.)  The biggest problem though is that in order to get an anti-inflammatory effect from N-3 use, is seems that at least 2 weeks oral supplementation is necessary to generate the appropriate changes in cell membrane phospholipid composition.
   
   
   
   
    
3. We think this because of some studies that were done using different ratios of n-6:n-3 PUFAs.   Ratios of 5:1, 10:1, 25:1, 50:1, & 100:1 were used. Then dogs got intradermal injections of lipopolysaccharide (endotoxin).  The skin area was removed & eicosenoids of various types were quantified.
   
   In the 5:1 group the desired leukotrienes were increased 79%.  In the 10:1 group they were increased 48%.  There were no signif. increases in the other groups. Similarly, the undesired thromboxanes were decreased the most in the 5:1 group, then in the 10:1 group, then not decreased in the other groups. 
   
   (It took 6 weeks on these ratios to see these changes in circulating cells, & 12 weeks to see these changes in skin.)
   
   
   
   
    
4. DVM markets dermcaps, dermcaps extra strength & a new product called 3V caps (I think- or something like that) which is hugely packed w/n-3 PUFAs. If it were a matter of eating tons of n-3s then it would be appropriate to buy these supplements.  Since it looks like there may be a ratio effect, diet comes into play. In order to control the n-6:n-3 ratio, dietary PUFAs must also be controlled.  (Every pet food has a different ratio so how would you know how much supplementation to take? You wouldn't.  The answer would be to set the desired ratio (whatever that is) in the pet food & not supplement at all.
   
   Of course, complicating the picture is that you may want a different ratio to effect inflammation in different organ systems. (one ratio for skin, another for renal effects, another for cardio etc.)  What a mess.
   
   
   
   
    
5. Kwashiorkor is protein restriction without severe caloric restriction whereas marasmus is protein deficiency WITH severe caloric restriction. In kwashiokor you get  decreased albumen & consequent edema/ascites & you also would tend to get a fatty liver. In marasmus you get decreased growth, reduced body weight & muscle atrophy.
   
   
   
   
    
6. Normally, when you are taught about essential amino acids, youget taught about the ones that area essential to humans.  The mnemonic device to remember these is Private Tim Hall (PVT TIM HALL). You are trying to remember: phenylalanine, valine, threonine, tryptophan, isoleucine, methionine, histidine, arginine, leucine, &lysine.  Some species diffs: taurine is essential for cats, arginine is not essential for all adult mammals (though it is certainly essential for growing ones & for cats.), glycine is essential for birds.